Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A non-randomized, open-label, multi-center, Phase I/II study of PI3K inhibitor copanlisib in pediatric patients with relapsed/refractory solid tumors or lymphoma

    Summary
    EudraCT number
    		 2017-000383-15
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    01 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2023
    First version publication date
    30 Jul 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BAY806946/19176
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03458728
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001757-PIP02-15
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Feb 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Phase 1: To establish the safety, maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of copanlisib in pediatric patients with a relapsed/refractory solid tumor or lymphoma. Phase 2: To determine the objective response rate (ORR) of copanlisib in pediatric patients with relapsed/refractory neuroblastoma, rhabdomyosarcoma or Ewing sarcoma. To determine the disease control rate (DCR) and progression free survival (PFS) in pediatric patients with relapsed/refractory osteosarcoma
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 31
    Worldwide total number of subjects
    31
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    14
    Adolescents (12-17 years)
    14
    Adults (18-64 years)
    3
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at 14 centers in United States between 30 APR 2018 (First subject first visit) and 05 JUL 2022 (Last subject last visit).

    Pre-assignment
    Screening details
    		 41 subjects were screened into the study (signed informed consent form (ICF)). 10 subjects were screening failed.

    Period 1
    Period 1 title
    Overall (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Copanlisib 28mg/m*2, Total
    Arm description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m*2, Total included AMD0 (5 subjects who were under the original DLT criteria) and AMD1+ (19 subjects who were under the amended DLT criteria).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Copanlisib
    Investigational medicinal product code
    BAY80-6946
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered on Day 1, Day 8 and Day 15 of every 28-day cycle.

    Arm title
    		 Copanlisib 35mg/m*2
    Arm description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Copanlisib
    Investigational medicinal product code
    BAY80-6946
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered on Day 1, Day 8 and Day 15 of every 28-day cycle.

    Number of subjects in period 1
    		Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Started
    24
    7
    Started treatment
    24
    7
    Terminated treatment
    24
    7
    Completed
    0
    0
    Not completed
    24
    7
         Physician decision
    1
    -
         Consent withdrawn by subject
    -
    1
         Adverse event, non-fatal
    1
    -
         Progressive disease - clinical assessment
    1
    -
         Progressive disease - radiological progression
    21
    6

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Copanlisib 28mg/m*2, Total
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m*2, Total included AMD0 (5 subjects who were under the original DLT criteria) and AMD1+ (19 subjects who were under the amended DLT criteria).

    Reporting group title
    Copanlisib 35mg/m*2
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.

    Reporting group values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2 Total
    Number of subjects
    		 24 7 31
    Age Categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 11 3 14
        Adolescents (12-17 years)
    		 10 4 14
        Adults (18-64 years)
    		 3 0 3
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.5 ( 4.6 ) 12.3 ( 3.8 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 10 3 13
        Male
    		 14 4 18
    Race
    Units: Subjects
        ASIAN
    		 1 2 3
        BLACK OR AFRICAN AMERICAN
    		 3 1 4
        NOT REPORTED
    		 3 1 4
        WHITE
    		 17 3 20
    Ethnicity
    Units: Subjects
        HISPANIC OR LATINO
    		 5 1 6
        NOT HISPANIC OR LATINO
    		 18 6 24
        NOT REPORTED
    		 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Copanlisib 28mg/m*2, Total
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m*2, Total included AMD0 (5 subjects who were under the original DLT criteria) and AMD1+ (19 subjects who were under the amended DLT criteria).

    Reporting group title
    Copanlisib 35mg/m*2
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects with at least one intake of study drug.

    Subject analysis set title
    Safety analysis set (SAF)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The SAF population was defined as all subjects with at least one intake of study drug.

    Subject analysis set title
    PK analysis set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects with at least one intake of study drug and with at least one valid measurement for copanlisib after first dosing were included in the copanlisib PK analysis.

    Subject analysis set title
    Copanlisib_Phase 1
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Copanlisib was administered on Day 1, Day 8, and Day 15 of every 28-day cycle. Subjects received copanlisib IV infusion with intermittent (3 weeks on / 1 week off) dosing schedule at the assigned dose level.

    Subject analysis set title
    Copanlisib_Phase 2
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    As the study was terminated before the initiation of phase 2, data was not collected in phase 2.

    Primary: Phase 1: Number of subjects with Dose limiting toxicity (DLT)

    		 Close Top of page
    End point title
    		 Phase 1: Number of subjects with Dose limiting toxicity (DLT) [1]
    End point description
    DLT was observed during first cycle of treatment, and assessed as possibly, probably or definitely related to treatment with copanlisib. The DLT observation period for the purposes of dose-escalation was the first cycle of therapy. DLT analysis was performed on SAF.
    End point type
    Primary
    End point timeframe
    Cycle 1
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All endpoints were analyzed using descriptive statistical methods.
    End point values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Number of subjects analysed
    24
    7
    Units: Subjects
    3
    2
    No statistical analyses for this end point

    Primary: Phase 1: The maximum tolerated dose (MTD): the highest dose level of copanlisib that can be given so that not more than 1 out of 6 patients experience a DLT during the DLT evaluation period.

    		 Close Top of page
    End point title
    		 Phase 1: The maximum tolerated dose (MTD): the highest dose level of copanlisib that can be given so that not more than 1 out of 6 patients experience a DLT during the DLT evaluation period. [2]
    End point description
    Maximum tolerated dose (MTD) for copanlisib was defined as the highest dose level where 6 patients have been treated and ≤ 1 participant experienced a DLT. This endpoint was performed on SAF.
    End point type
    Primary
    End point timeframe
    Cycle 1 (28 days)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All endpoints were analyzed using descriptive statistical methods.
    End point values
    		 Copanlisib_Phase 1
    Number of subjects analysed
    31
    Units: mg/m*2/d
        number (not applicable)
    28
    No statistical analyses for this end point

    Primary: Phase 1: Number of subjects with Treatment-emergent adverse events (TEAEs)

    		 Close Top of page
    End point title
    		 Phase 1: Number of subjects with Treatment-emergent adverse events (TEAEs) [3]
    End point description
    TEAE was defined as any event arising or worsening after start of study drug administration until 30 days after the last dose of the study drug intake (end of safety follow-up). This endpoint was performed on SAF.
    End point type
    Primary
    End point timeframe
    After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 145 days.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All endpoints were analyzed using descriptive statistical methods.
    End point values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Number of subjects analysed
    24
    7
    Units: Subjects
    24
    7
    No statistical analyses for this end point

    Primary: Phase 1: Number of subjects with Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Phase 1: Number of subjects with Serious Adverse Events (SAEs) [4]
    End point description
    This endpoint was performed on SAF.
    End point type
    Primary
    End point timeframe
    Up to 150 days.
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All endpoints were analyzed using descriptive statistical methods.
    End point values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Number of subjects analysed
    24
    7
    Units: Subjects
    10
    0
    No statistical analyses for this end point

    Primary: Phase 1: Number of participants with Treatment-related Adverse Events (AEs).

    		 Close Top of page
    End point title
    		 Phase 1: Number of participants with Treatment-related Adverse Events (AEs). [5]
    End point description
    This endpoint was performed on SAF.
    End point type
    Primary
    End point timeframe
    Up to 145 days.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: All endpoints were analyzed using descriptive statistical methods.
    End point values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Number of subjects analysed
    24
    7
    Units: Subjects
    5
    0
    No statistical analyses for this end point

    Primary: Phase 2: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Phase 2: Progression-free survival (PFS) [6]
    End point description
    End point type
    Primary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [7]
    Units: Subjects
    Notes
    [7] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Primary: Phase 2: Disease control rate (DCR)

    		 Close Top of page
    End point title
    		 Phase 2: Disease control rate (DCR) [8]
    End point description
    The DCR was defined as the number of subjects with disease control divided by the number of subjects in FAS or per protocol set (PPS) in the indication.
    End point type
    Primary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [9]
    Units: Subjects
    Notes
    [9] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Primary: Phase 2: Objective response rate (ORR)

    		 Close Top of page
    End point title
    		 Phase 2: Objective response rate (ORR) [10]
    End point description
    ORR was defined separately in each indication, as the number of responders divided by the number of subjects in FAS in the indication.
    End point type
    Primary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [11]
    Units: Subjects
    Notes
    [11] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 1: Copanlisib maximum drug concentration (Cmax)

    		 Close Top of page
    End point title
    		 Phase 1: Copanlisib maximum drug concentration (Cmax)
    End point description
    Cmax: maximum concentration after the 3rd dose in a sequence of 3 nominal doses of 28 mg/m2 [each dose infused over 1 hour at 168-hour interval] Cmax analysis was performed on PK analysis set.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Day 15
    End point values
    		 Copanlisib_Phase 1
    Number of subjects analysed
    30
    Units: μg/L
        geometric mean (geometric coefficient of variation)
    359 ( 22.6 )
    No statistical analyses for this end point

    Secondary: Phase 1: Area under the curve (AUC(0-168))

    		 Close Top of page
    End point title
    		 Phase 1: Area under the curve (AUC(0-168))
    End point description
    AUC(0-168): Area under the concentration-time curve [AUC] from 0 to 168 hours after the 3rd dose in a sequence of 3 nominal doses of 28 mg/m2 [each dose infused over 1 hour at 168-hour interval]. AUC(0-168) analysis was performed on PK analysis set.
    End point type
    Secondary
    End point timeframe
    On cycle 1, day 1 (C1D1) and cycle 1, day 15 (C1D15)
    End point values
    		 Copanlisib_Phase 1
    Number of subjects analysed
    30
    Units: μg∙h/L
        geometric mean (geometric coefficient of variation)
    2900 ( 35.4 )
    No statistical analyses for this end point

    Secondary: Phase 1: Objective response rate (ORR)

    		 Close Top of page
    End point title
    		 Phase 1: Objective response rate (ORR)
    End point description
    ORR by dose cohort is defined as the number of responders divided by the number of subjects in FAS in the indication. The analysis of ORR was performed on FAS.
    End point type
    Secondary
    End point timeframe
    Up to 150 days
    End point values
    		 Copanlisib 28mg/m*2, Total Copanlisib 35mg/m*2
    Number of subjects analysed
    24
    7
    Units: Subjects
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of response (DOR)

    		 Close Top of page
    End point title
    		 Phase 2: Duration of response (DOR)
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [12]
    Units: Subjects
    Notes
    [12] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 2: PFS in each indication except for osteosarcoma

    		 Close Top of page
    End point title
    		 Phase 2: PFS in each indication except for osteosarcoma
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [13]
    Units: Subjects
    Notes
    [13] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 2: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Phase 2: Overall survival (OS)
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [14]
    Units: Subjects
    Notes
    [14] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 2: Number of participants with Treatment-emergent AEs

    		 Close Top of page
    End point title
    		 Phase 2: Number of participants with Treatment-emergent AEs
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [15]
    Units: Subjects
    Notes
    [15] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 2: Number of subjects with treatment emergent SAEs

    		 Close Top of page
    End point title
    		 Phase 2: Number of subjects with treatment emergent SAEs
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [16]
    Units: Subjects
    Notes
    [16] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Secondary: Phase 2: Number of subjects with treatment-emergent clinically significant change in laboratory parameters, ECGs and vital signs

    		 Close Top of page
    End point title
    		 Phase 2: Number of subjects with treatment-emergent clinically significant change in laboratory parameters, ECGs and vital signs
    End point description
    End point type
    Secondary
    End point timeframe
    Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
    End point values
    		 Copanlisib_Phase 2
    Number of subjects analysed
    0 [17]
    Units: Subjects
    Notes
    [17] - Data was not collected due to termination of phase 2.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 145 days. Death (all-cause) were collected with a maximum of 150 days.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Copanlisib 35mg/m*2
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease,unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol.

    Reporting group title
    Copanlisib 28mg/m*2, Total
    Reporting group description
    		 Copanlisib was administered Intravenous (IV) on Days 1, 8 and 15 of each 28-day treatment cycle. Treatment was continued until radiological progressive disease, unacceptable toxicity, withdrawal of consent, death or other event specified by the protocol. Copanlisib 28mg/m*2, Total included AMD0 (5 subjects who were under the original DLT criteria) and AMD1+ (19 subjects who were under the amended DLT criteria)

    Serious adverse events
    		 Copanlisib 35mg/m*2 Copanlisib 28mg/m*2, Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 7 (0.00%)
    10 / 24 (41.67%)
         number of deaths (all causes)
    5
    20
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Spinal cord compression
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 24 (20.83%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Copanlisib 35mg/m*2 Copanlisib 28mg/m*2, Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    23 / 24 (95.83%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 7 (28.57%)
    10 / 24 (41.67%)
         occurrences all number
    2
    42
    Hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    7 / 24 (29.17%)
         occurrences all number
    2
    7
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 7 (42.86%)
    10 / 24 (41.67%)
         occurrences all number
    7
    14
    Gait disturbance
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    4 / 7 (57.14%)
    8 / 24 (33.33%)
         occurrences all number
    7
    19
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 24 (16.67%)
         occurrences all number
    1
    5
    Vessel puncture site pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Throat irritation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Tachypnoea
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 24 (12.50%)
         occurrences all number
    2
    4
    Pleural effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Nasal congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Hypoxia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    5 / 24 (20.83%)
         occurrences all number
    2
    7
    Cough
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 24 (25.00%)
         occurrences all number
    1
    7
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Irritability
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Insomnia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    Hallucination
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Depression
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Anxiety
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Agitation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 24 (25.00%)
         occurrences all number
    0
    6
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 24 (25.00%)
         occurrences all number
    2
    8
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 7 (28.57%)
    6 / 24 (25.00%)
         occurrences all number
    2
    11
    Blood cholesterol increased
         subjects affected / exposed
    1 / 7 (14.29%)
    5 / 24 (20.83%)
         occurrences all number
    1
    5
    Blood creatinine increased
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 24 (16.67%)
         occurrences all number
    4
    4
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 24 (20.83%)
         occurrences all number
    0
    6
    C-reactive protein increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Carbon dioxide decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    8
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    High density lipoprotein decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    International normalised ratio increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Lipase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    5 / 24 (20.83%)
         occurrences all number
    0
    7
    Lymphocyte count decreased
         subjects affected / exposed
    3 / 7 (42.86%)
    13 / 24 (54.17%)
         occurrences all number
    7
    35
    Neutrophil count decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    6 / 24 (25.00%)
         occurrences all number
    9
    14
    Neutrophil count increased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Protein total decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Weight decreased
         subjects affected / exposed
    2 / 7 (28.57%)
    3 / 24 (12.50%)
         occurrences all number
    3
    6
    White blood cell count decreased
         subjects affected / exposed
    5 / 7 (71.43%)
    12 / 24 (50.00%)
         occurrences all number
    7
    21
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    4 / 24 (16.67%)
         occurrences all number
    1
    4
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Thermal burn
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 24 (8.33%)
         occurrences all number
    2
    2
    Pericardial effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Sinus tachycardia
         subjects affected / exposed
    3 / 7 (42.86%)
    6 / 24 (25.00%)
         occurrences all number
    4
    7
    Nervous system disorders
    Tremor
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    9 / 24 (37.50%)
         occurrences all number
    3
    11
    Dizziness
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Somnolence
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    3 / 7 (42.86%)
    7 / 24 (29.17%)
         occurrences all number
    4
    21
    Anaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    13 / 24 (54.17%)
         occurrences all number
    8
    38
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 7 (57.14%)
    15 / 24 (62.50%)
         occurrences all number
    7
    22
    Oral pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 7 (57.14%)
    7 / 24 (29.17%)
         occurrences all number
    12
    11
    Hypoaesthesia oral
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    2 / 7 (28.57%)
    8 / 24 (33.33%)
         occurrences all number
    3
    8
    Constipation
         subjects affected / exposed
    4 / 7 (57.14%)
    4 / 24 (16.67%)
         occurrences all number
    4
    6
    Abdominal pain
         subjects affected / exposed
    2 / 7 (28.57%)
    5 / 24 (20.83%)
         occurrences all number
    2
    9
    Abdominal distension
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Skin and subcutaneous tissue disorders
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Pruritus
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Pain of skin
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    2 / 7 (28.57%)
    8 / 24 (33.33%)
         occurrences all number
    2
    12
    Neck pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    Myalgia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Back pain
         subjects affected / exposed
    1 / 7 (14.29%)
    7 / 24 (29.17%)
         occurrences all number
    1
    12
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    6 / 24 (25.00%)
         occurrences all number
    0
    7
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Hyperglycaemia
         subjects affected / exposed
    4 / 7 (57.14%)
    17 / 24 (70.83%)
         occurrences all number
    8
    44
    Hyperkalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    5
    Hypermagnesaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 24 (25.00%)
         occurrences all number
    1
    7
    Hyperphosphataemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 24 (12.50%)
         occurrences all number
    2
    3
    Hyperuricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Decreased appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 24 (25.00%)
         occurrences all number
    4
    8
    Hypouricaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Hypophosphataemia
         subjects affected / exposed
    1 / 7 (14.29%)
    7 / 24 (29.17%)
         occurrences all number
    1
    11
    Hyponatraemia
         subjects affected / exposed
    2 / 7 (28.57%)
    11 / 24 (45.83%)
         occurrences all number
    3
    16
    Hypokalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    8
    Hypoglycaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    10
    Hypocalcaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    8 / 24 (33.33%)
         occurrences all number
    0
    12
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 7 (28.57%)
    10 / 24 (41.67%)
         occurrences all number
    2
    16

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Apr 2019
    The primary driver of this protocol amendment was the amendment to DLT criteria. Under the previous version of the protocol, DLTs were not graded based on clinical significance of the AE but rather on numerical values (e.g., lab values that were not considered clinically significant enough to be considered truly dose-limiting) and both Sponsor and investigators considered that it was not reflective of the true safety profile of the study drug. Therefore, this amendment revised the DLT criteria to reflect what would be considered truly dose-limiting maintaining the safety of the patients but allowing for more flexibility to dose patients in this population of high unmet medical need. Additional changes were made to make the dose modification consistent with the updated DLT criteria.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon May 06 11:03:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA